Glycan structure and complexity

'an' stands for polysaccharide (sugar),

its nomenclature

Does genome size correlate with complexity of an

organism?
Organism

Est size
(bp)

Est gene
#

Mean gene density

Chromosome
#

human 3.2 x 109

~ 25 K

1 gene
per 100 K bases

46

2.6 x 109

~ 25 K

1 gene
per 100 K bases

40

Fruit fly 137 x 106

13 K

1 gene
per 9 K bases

97 x 106

19 K

1 gene
per 5 K bases

12

12 x 106

6K

1 gene
per 2 K bases

32

mouse

Round
worm
yeast

Genome size does not correlate with complexity of the organism.

The number of genes is not proportionate with genome size.
http://www.ornl.gov/sci/

Genomics

Genes, deoxyribonucleic acid (DNA) sequence at the organismal level

Intra-organismal cell-specific variations

Proteomics

Proteins and peptides, at levels of the organism, the tissue, or the cell

Post-translational modifications

Glycomics

Glycans, at levels of the organism, the tissue, or the cell

It is dynamic
State 1 State 2
Embryonic stem cell
Differentiated cell
Normal cell
Cancer cell
Healthy cell
Injured cell

Where in the cell are glycans and

glycoconjugates localized ?
What are their functions at these localities?
What properties are required for these
functions?
What molecular features support these
properties?

Glycans are exposed to the

extracellular environment
Glycoproteins
Glycolipids

Lectin-saccharide
interactions

Kd = 10-6 - 10-7 mol/L,

weaker than Ag-Ab
interactions

Glycoproteins &
Glycolipids
QC, trafficking, sorting
Cell-cell adhesion
Cell-cell interaction
fertilization
immunity
infection
cancer

Different blood
types due to
presence of
different types of
glycans

In type B, galactose
linked to galactose

Cell surface proteoglycans

Proteoglycans in the extracellular matrix

Glycosminoglycans
DRUs tetrasaccharide - serine

Structural polysaccharides
Glycans
Cellulose

Chitin
Glycosaminoglycans
hyaluronan

Bonds between
saccharide units
-1,4 glycosidic bond
linking Glc residues

Form

-1,4 glycosidic bond

linking GlcNAc res

Linear

Linear

Linear
Disaccharide repeats of
GlcUA and GlcNAc,
linked via alternating 1,4 and -1,3 glycosidic
bonds

Storage polysaccharides energy store

Glucans

Starch
amylose

Bonds between glc

residues

Form

-1,4 glycosidic bond linear

Repeating
glc units
1000
4000

-1,4 glycosidic bond Linear

amylopectin -1,6 glycosidic bond branched

20 25 per
segment

-1,4 glycosidic bond Linear

-1,6 glycosidic bond branched

12 18 per
segment

Glycogen

A segment of amylose

A segment of amylopectin

What strategies are used to release

glucose units from
dietary vs stored glycogen?

Extracellular digestion ()

Intracellular digestion (, , )

Enzymatic cleavage

starch can be used as storage molecule as it has many enzyme

cleavage site. It has many reducing ends which can be
attacked to release glucose..... helps break up food

Fates of digestion products

Glucose from amylase action in gut lumen

Intestinal absorption, delivery via hepatic portal vein

Transport into hepatocytes
In hepatocytes, glycolysis .ATP
or glycogenesis ..storage in cells

Glucose 1-phosphate, from glycogen

phosphorylase action in liver cells or
myocytes

Isomerization to Glc 6-phosphate, then glycolysis

ATP

Back to Basics

Monosaccharides

Glucose, galactose, mannose

Fructose

Aldohexoses aldehyde group at C-1

Glc and man epimeric at C-2
Glc and gal epimeric at C-4
Ketohexose ketone group at C-2
Glc and fru are structural isomers.

Ribose

Aldopentose aldehyde group at C-1

..linking by glycosidic bonds

not covered in lecture

Towards new therapeutics

Infection by influenza virus

Drugs that inhibit neuraminidase prevent

propagation of the virus

Inflammatory diseases

Drugs to perturb selectin-sugar ligand

interactions interfere with recruitment of
leukocytes

not covered in
lecture

Influenza virus and therapeutic targets (1)

Hemagglutinin (HA)

HA binds to sialic acid residues on

surface glycoproteins of host cells and
triggers internalization of virus

Neuraminadase (NA)

NA cleaves sialic acid residues off

surface glycoproteins of host cells and
faciliatates viral propagation

M2 Ion Channel

Proton-selective ion channel lowers

the pH inside of the virus resulting in
dissociation of the RNPs from the
matrix protein (M1)

Ribonucleoprotein (RNP)

www.cdc.gov/h1n1flu/yearinreview/yir1.htm

An independent transcription active

unit (containing a polymerase complex)
packaged in nucleoprotein

not covered in lecture

Haemaglutinin binds sialic

acid residues on host cell
surface glycoproteins

Neuraminidase cleaves sialic

acid residues off host cell
surface glycoproteins

Mukhopadhyay et al. Nature Reviews Microbiology 3, 13-22 (2005)

Influenza virus targets of therapeutic intervention

not covered in
lecture

Amantadine

Amantadine

Ribavarin

von Itzstein Nature Reviews Drug Discovery

6, 967-974 (2007)

Zanamivir,
oseltamivir

O-linked glycans
not covered in
lecture

not covered in
lecture

(1)

(2)

not covered in
lecture